PDF herunterladen
Horm Metab Res 2004; 36(4): 210-214
DOI: 10.1055/s-2004-814449
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Signals in the Activation of Opioid µ-Receptors by Loperamide to Enhance Glucose Uptake into Cultured C2C12 Cells

I.  M.  Liu1 , S.  S.  Liou1 , W.  C.  Chen2 , P.  F.  Chen3 , J.  T.  Cheng3
  • 1The Department of Pharmacy, Tajen Institute of Technology, Yen-Pou, Ping Tung Shien, Taiwan 90701, R.O.C.
  • 2The Department of Chinese Medicine, Jin-Ai Municipal Hospital, Taipei City, Taiwan 10501, R.O.C.
  • 3The Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, R.O.C.
Weitere Informationen

Publikationsverlauf

Received 12 August 2003

Accepted without Revision 10 November 2003

Publikationsdatum:
28. April 2004 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

In an attempt to understand the signal pathways of opioid µ-receptors for glucose metabolism, we used loperamide to investigate the glucose uptake into the myoblast C2C12 cells. Loperamide enhanced the uptake of radioactive deoxyglucose into C2C12 cells in a concentration-dependent manner that was abolished in cells pre-incubated with naloxone or naloxonazine at concentrations sufficient to block opioid µ-receptors. Pharmacological inhibition of phospholipase C (PLC) by U73122 resulted in a concentration-dependent decrease in loperamide-stimulated uptake of radioactive deoxyglucose into C2C12 cells. This inhibition of glucose uptake by U73122 was specific since the inactive congener, U73343, failed to modify loperamide-stimulated glucose uptake. Moreover, both chelerythrine and GF 109203X diminished the action of loperamide at concentrations sufficient to inhibit protein kinase C (PKC). The obtained data suggest that an activation of opioid µ-receptors in C2C12 cells by loperamide may increase glucose uptake via the PLC-PKC pathway.

Key words

C2C12 cells - Loperamide - Opioid µ-receptors - Phospholipase C - Protein kinase C

References

  • 1 Chevlen E. Opioids: a review.  Current Pain & Headache Reports. 2003;  7 15-23
    PubMedSuche in Google Scholar
  • 2 Yaksh T L. Pharmacology and mechanisms of opioid analgesic activity.  Acta anaesthesiol Scand. 1997;  41 94-111
    PubMedSuche in Google Scholar
  • 3 Smith E M. Opioid peptides in immune cells.  Advances in Experimental Medicine & Biology. 2003;  521 51-68
    PubMedSuche in Google Scholar
  • 4 Curry D L, Li C H. Stimulation of insulin secretion by β-endorphin (1 - 27 and 1 - 31).  Life Sci. 1987;  40 2053-2058
    CrossrefPubMedSuche in Google Scholar
  • 5 Locatelli A, Spotti D, Caviezel F. The regulation of insulin and glucagon secretion by opiates: a study with naloxone in healthy humans.  Acta Diabetol. 1985;  22 25-31
    PubMedSuche in Google Scholar
  • 6 Khawaja X Z, Green I C, Thorpe J R, Titheradge M A. The occurrence and receptor specificity of endogenous opioid peptides with pancreas and liver of the rat. Comparison with brain.  Biochem J. 1990;  267 233-240
    PubMedSuche in Google Scholar
  • 7 Cheng J T, Liu I M, Tzeng T F, Tsai C C, Lai T Y. Plasma glucose lowering effect of β-endorphin in streptozotocin-induced diabetic rats.  Horm Meta Res. 2002;  34 570-576
    Thieme ConnectPubMedSuche in Google Scholar
  • 8 Cheng J T, Liu I M, Tzeng T F, Chen W C, Hayakawa S, Yamamoto T. Release of β-endorphin by caffeic acid to lower plasma glucose in streptozotocin-induced diabetic rats.  Horm Metab Res. 2003;  35 251-258
    Thieme ConnectPubMedSuche in Google Scholar
  • 9 Liu I M, Chi T C, Chen Y C, Lu F H, Cheng J T. Activation of opioid µ-receptor by loperamide to lower plasma glucose in streptozotocin-induced diabetic rats.  Neurosci Lett. 1999;  265 183-186
    CrossrefPubMedSuche in Google Scholar
  • 10 Tzeng T F, Liu I M, Lai T Y, Tsai C C, Chang W C, Cheng J T. Loperamide increases glucose utilization in streptozotocin-induced diabetic rats.  Clin Exp Pharmacol Physiol. 2003;  30 734-738
    CrossrefPubMedSuche in Google Scholar
  • 11 Sheriff S, Fischer J E, Balasubramaniam A. Amylin inhibits insulin-stimulated glucose uptake in C2C12 muscle cell line through a cholera-toxin-sensitive mechanism.  Biochim Biophys Acta. 1992;  1136 219-222
    PubMedSuche in Google Scholar
  • 12 Liu I M, Tsai C C, Lai T Y, Cheng J T. Stimulatory effect of isoferulic acid on alpha1A-adrenoceptor to increase glucose uptake into cultured myoblast C2C12 cell of mice.  Auton Neurosci Basic & Clinic. 2001;  88 175-180
    PubMedSuche in Google Scholar
  • 13 Heel R C, Brogden R N, Speight T M, Avery G S. Loperamide: a review of its pharmacological properties and therapeutic efficacy in diarrhea.  Drugs. 1978;  15 33-52
    PubMedSuche in Google Scholar
  • 14 Crist G H, Xu B, Lanoue F, Lang C H. Tissue-specific effects of in vivo adenosine receptor blocked on glucose uptake in Zucker rats.  FASEB J. 1998;  12 1301-1308
    PubMedSuche in Google Scholar
  • 15 Martin W R. Opioid antagonists.  Pharmacol Rev. 1967;  19 463-521
    PubMedSuche in Google Scholar
  • 16 Ling G SF, Simantov R, Clark J A, Pasternak G W. Naloxonazine actions in vivo.  Eur J Pharmacol. 1986;  129 33-38
    CrossrefPubMedSuche in Google Scholar
  • 17 Evans A A, Hughes S, Smith M E. Delta-opioid peptide receptors in muscles from obese diabetic and normal mice.  Peptides. 1995;  16 361-364
    CrossrefPubMedSuche in Google Scholar
  • 18 Ishizuka T, Cooper D R, Hernandez H, Buckley D, Standaert M, Farese R V. Effects of insulin on diacylglycerol-protein kinase C signaling in rat diaphragm and soleus muscles and relationship to glucose transport.  Diabetes. 1990;  39 181-190
    CrossrefPubMedSuche in Google Scholar
  • 19 Van Epps-Fung M, Gupta K, Hardy R W, Wells A. A role for phospholipase C activity in GLUT4-Mediated glucose transport.  Endocrinology. 1997;  138 5170-5175
    CrossrefPubMedSuche in Google Scholar
  • 20 Wasserman D H, Zinman B. Exercise in individuals with IDDM.  Diabetes Care. 1994;  17 924-937
    CrossrefPubMedSuche in Google Scholar
  • 21 Cheng J T, Liu I M, Chi T C, Tzeng T F, Lu F H, Chang C J. Plasma glucose lowering effect of tramadol in streptozotocin-induced diabetic rats.  Diabetes. 2001;  50 2815-2821
    PubMedSuche in Google Scholar
  • 22 Xie W, Samoriski G M, McLaughlin J P, Romoser V A, Smrcka A, Hinkle P M, Bidlack J M, Gross R A, Jiang H, Wu D. Genetic alteration of phospholipase C β3 expression modulates behavioral and cellular responses to mu opioids.  Proc Natl Acad Sci USA. 1999;  96 10 385-10 390
    PubMedSuche in Google Scholar
  • 23 Smallridge R C, Kiang J G, Gist I D, Fein H G, Gallowat R J. U-73 122, an aminosteroid phospholipase C antagonist, noncompetitively inhibits thyrotropin-releasing hormone effects in GH3 rat pituitary cell.  Endocrinology. 1992;  131 1883-1888
    CrossrefPubMedSuche in Google Scholar
  • 24 Muto Y, Nagao T, Urushidani T. The putative phospholipase C inhibitor U73122 and its negative control, U73343, elicit unexpected effects on the rabbit parietal cell.  J Pharmac Exp Ther. 1997;  282 1379-1388
    PubMedSuche in Google Scholar
  • 25 Herbert J M, Augereau J M, Gleye J, Maffrand J P. Chelerythrine is a potent and specific inhibitor of protein kinase C.  Biochem Biophys Res Commun. 1990;  172 993-999
    CrossrefPubMedSuche in Google Scholar
  • 26 Toullec D, Pianetti P, Coste H, Bellevergue P, Grand-Perret T, Ajakane M, Baudent V, Boissin P, Boursier E, Loriolle F, Duhamel L, Charon D, Kirilovsky J. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C.  J Biol Chem. 266;  1991 15 771-15 781
    PubMedSuche in Google Scholar
  • 27 Narita M, Ohnishi O, Nemoto M, Aoki T, Suzuki T. The involvement of phosphoinositide 3-kinase (PI3-Kinase) and phospholipase C gamma (PLC gamma) pathway in the morphine-induced supraspinal antinociception in the mouse.  Nihon Shinkei Seishin Yakurigaku Zasshi. 2001;  21 7-14
    PubMedSuche in Google Scholar
  • 28 Freye E, Latasch L. Development of opioid tolerance - molecular mechanisms and clinical consequences.  Anasthesiol Intensivmed Notfallmed Schmerzther. 2003;  38 14-26
    Thieme ConnectPubMedSuche in Google Scholar
  • 29 Neri L M, Borgatti P, Capitani S, Martelli A M. Protein kinase C isoforms and lipid second messengers: a critical nuclear partnership?.  Histol Histopath. 2002;  17 1311-1316
    PubMedSuche in Google Scholar
  • 30 Bandyopadhyay G, Standaert M L, Kikkawa U, Ono Y, Moscat J, Farese R V. Effects of transiently expressed atypical (zeta, lambda), conventional (alpha, beta) and novel (delta, epsilon) protein kinase C isoforms on insulin-stimulated translocation of epitope-tagged GLUT4 glucose transporters in rat adipocytes: specific interchangeable effects of protein kinases C-zeta and C-lambda.  Biochem J. 1999;  337 461-370
    CrossrefPubMedSuche in Google Scholar

Prof. J.-T. Cheng

Department of Pharmacology · College of Medicine · National Cheng Kung University

Tainan City · Taiwan 70101 · R.O.C.

Telefon: +886(6)2372706

Fax: +886(6)2386548 ·

eMail: jtcheng@mail.ncku.edu.tw